The overall goal of this work is to develop functional magnetic resonance and optical imaging techniques that allow non-invasive assessment of brain and heart function. A secondary goal is to combine moelcular genetics with non-invasive imaging to understand cellular energetics and the role of the enzyme creatine kinase. Over the past year we have installed and made operational an 11.7 Tesla MRI for animals This very high field MRI is enabling extension of MRI spatial resolution and sensitivity of functional MRI. In addition, the new Mouse Imaging Facility has become operational under our guidance. Imaging devices include high frequency ultra-sound, CT, and MRI. Another addition to the In Vivo NMR Center to house a NIMH/NINDS 3T human MRI and a NINDS/NIMH 7T MRI is nearing completion. The 3T is being delivered and the 7T is expected to arrive in the summer of 2002. Scientifically, progress has been made on three fronts. Functional MRI technqiues are having a broad impact on understanding brain. We have demonstrated in the rodent brain that with very high temporal and spatial resolution specific layers in the mammalian cortex can be defined. This opens the possibilities of studying the specific route of communication from different cortical regions during plasticity and learning. We have continued to develop the use of manganese ion as a functional MRI contrast agent to assess calcium influx and to trace neuronal connections in vivo. Recent work demonstrates that we can detect activation of specific areas of the olfactory bulb due to specific odors in mice and track the connections of these olfatory bulb regions to the primary olfactory cortex using MRI. Over the past year we have demonstrated that manganese enhanced MRI can also distinguish cortical layers and can be used to trace neuronal connections from the peripheral nervous system. In the heart, we have demonstrated that manganese accumulation can be detected by MRI and is proportional to calcium influx rate during different inotropic states. Results indicate that manganese can distingusih ischemic areas. Finally, we have an exciting finding that the mitochondrial isoform of creatine kinase protects transgenic mouse liver and mice from septic shock. This combined with previous results that the mitochondiral isoform of creatine kinase can inhibit liver regeneration clearly indicates a role for creatine kinase in cell death and cell division. We have used two dimensional gel electrophoresis technqiues to study changes in mitochondrial proteins that occur due to loss of creatine kinase. A major change in aconitase has led to the theory that mitochondrial creatine kinase plays a role in free radical metabolism. this may explain the effects of mitochondrial creatine kinase on liver.